Journal
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
Volume 57, Issue 8, Pages 517-524Publisher
WILEY-BLACKWELL
DOI: 10.1002/jlcr.3207
Keywords
NMR; hyperpolarization; contrast agent; phospholactate; parahydrogen
Funding
- NIH [5R00 CA134749-03, 3R00CA134749-02S1, S10 RR019022]
- DoD CDMRP Breast Cancer Program Era of Hope Award [W81XWH-12-1-0159/BC112431]
- NIH/NCI [R01CA160700]
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Here, we present a new approach for the delivery of a metabolic contrast agent for in vivo molecular imaging. The use of a phosphate-protecting group that facilitates parahydrogen-induced polarization of 1-C-13-phospholactate potentially enables the in vivo administration of a hydrogenated hyperpolarized adduct. When injected, nonhyperpolarized 1-C-13-phospholactate is retained in the vasculature during its metabolic conversion to 1-C-13-lactate by blood phosphatases as demonstrated here using a mucin 1 mouse model of breast cancer and ex vivo high-resolution C-13 NMR. This multisecond process is a suitable mechanism for the delivery of relatively short-lived C-13 and potentially N-15 hyperpolarized contrast agents using -OH phosphorylated small molecules, which is demonstrated here for the first time as an example of 1-C-13-phospholactate. Through this approach, DL-1-C-13-lactate is taken up by tissues and organs including the liver, kidneys, brain, heart, and tumors according to a timescale amenable to hyperpolarized magnetic resonance imaging.
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